近日，美国威斯康星大学麦迪逊分校Ci Ji Lim及其小组解析与端粒模板结合的人类CST-Polα-primase复合物结构。这一研究成果于2022年7月13日在线发表在国际学术期刊《自然》上。

Author: He, Qixiang, Lin, Xiuhua, Chavez, Bianca L., Agrawal, Sourav, Lusk, Benjamin L., Lim, Ci Ji

Issue&Volume: 2022-07-13

Abstract: The mammalian DNA polymerase-alpha/primase (pol-α/primase) is essential for DNA metabolism, providing the de novo RNA-DNA primer for several DNA replication pathways1-4 such as lagging-strand synthesis and telomere C-strand fill-in. The underlying physical mechanism of how pol-α/primase, alone or in partnership with accessory proteins, performs its complicated multistep primer synthesis function is unknown. Here, we show that CST, a single-stranded DNA-binding accessory protein complex of pol-α/primase, physically sets up the enzyme for efficient primer synthesis. Cryo-electron microscopy structures of CST-pol-α/primase preinitiation complex (PIC) bound to various types of telomere overhang reveal template-bound CST partitions the DNA and RNA catalytic centers of pol-α/primase into two separate domains and effectively arrange them in RNA-DNA synthesis order. The PIC architecture provides a single solution for the multiple structural needs for pol-α/primase RNA-DNA primer synthesis. Multiple insights into CST template-binding specificity, template requirement for CST-pol-α/primase PIC assembly, and activation are also revealed in this study.

DOI: 10.1038/s41586-022-05040-1

Source: https://www.nature.com/articles/s41586-022-05040-1